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ADULT UROLOGY
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SELECTIVE ABLATION OF SYMPTOMATIC DOMINANTRENAL CYSTS USING 99% ETHANOL IN ADULT
POLYCYSTIC KIDNEY DISEASE
IQBAL SINGH AND GOPESH MEHROTRA
ABSTRACTbjectives. To evaluate the clinical efficacy and outcome of 99% ethanol as a sclerosing agent for managing
hronic flank pain due to dominant cysts in selected patients with adult polycystic kidney disease. Tradi-ionally, such patients have been treated with analgesics and surgical/laparoscopic deroofing. Cyst aspirationclerotherapy is a minimally invasive therapeutic option for such patients, and limited published data existn this subject. This formed the basis for the present study.ethods. A pilot study was undertaken during a 1-year period to evaluate the clinical efficacy of ultrasound-
uided cyst aspiration-ethanol injection sclerotherapy in 15 preselected patients with diagnosed adultolycystic kidney disease. All punctures were performed with strict aseptic precautions and local anesthesian an outpatient basis. The patients were evaluated with serial scans, pain scores, and serum creatininealues.esults. A total of 48 dominant cysts were successfully treated in all 15 patients with regard to cystspiration and shrinkage. At the end of 1 year, the pain and dominant cysts had completely disappeared in3 patients and had recurred in 2; repeat cyst aspiration and sclerotherapy was done in 3 patients.ephrocutaneous fistula and urinary tract infection occurred in 1 patient each. The decrease in the paincore and the rise in the serum creatinine level were statistically significant at P �0.05 and P �0.001,espectively.onclusions. Alcohol cyst sclerotherapy is a minimally invasive, safe, and effective alternative to conven-ional surgical/laparoscopic deroofing for managing chronic flank pain due to adult polycystic kidney diseasen selected patients. It should be considered as a safe and viable therapeutic option in patients in whom therimary symptom is chronic flank pain due to one or more dominant cysts. UROLOGY 68: 482–488, 2006.2006 Elsevier Inc.
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dult autosomal-dominant polycystic kidney dis-ease (ADPKD) is an autosomal dominant disor-
er present in approximately 1:500 to 1:1000 liveirths1 and in 10% to 12% of end-stage renal disease,aking it the most common hereditary disease.2 Pa-
ients with ADPKD are frequently crippled by severe,ecurrent, and often persistent flank pain that doesot resolve despite adequate analgesics. Treatmentptions are limited to open/laparoscopic deroofing of
rom the Departments of Surgery (Division of Urology), andadiology, University College of Medical Sciences, University ofelhi and GTB Hospital, New Delhi, IndiaReprint requests: Iqbal Singh, M.Ch.(Urology), Division of
rology, Department of Surgery, University College of Medi-al Sciences, University of Delhi and GTB Hospital, F-14outh Extension Part-2, New Delhi 110049, India. E-mail:[email protected]
Submitted: October 21, 2005, accepted (with revisions): March
i1, 2006© 2006 ELSEVIER INC.82 ALL RIGHTS RESERVED
he dominant or multiple cysts, which is invasive,equires hospitalization, and administration of gen-ral anesthesia. Cyst aspiration and sclerotherapy is aelatively newer emerging minimally invasive optionor ADPKD. Sclerotherapy can be easily accom-lished under local anesthesia with ultrasound-uided cyst aspiration-injection as an outpatient sur-ical procedure. We evaluated the role, outcome, andesults of using 95% absolute ethanol in 15 selectedymptomatic patients with ADPKD.
MATERIAL AND METHODS
A pilot study was undertaken in 15 preselected patientsith ADPKD. The selection criteria included patients withiagnosed ADPKD and ultrasound (US), intravenous urogra-hy (IVU), or contrast-enhanced computed tomographyCECT) evidence of noncommunicating dominant cysts; se-ere flank pain; and normal renal function test results. Dom-
nant cysts were defined as those larger than 5 cm and causing0090-4295/06/$32.00doi:10.1016/j.urology.2006.03.080
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evere flank pain with pressure signs on the IVU or CECTcan. Patients with advanced chronic renal insufficiency, non-ominant renal cysts, hypertension, hematuria, and/or clini-ally significant urosepsis were excluded from the presenttudy. All patients were fully counseled and gave informedonsent before cyst sclerotherapy. Before the procedure, allatients had undergone urinalysis or urine culture; renal func-ion tests; US of the pelvic, abdominal, bladder region; IVU;ECT; and a coagulation profile, without exception. All pa-
ients were premedicated with intramuscular diclofenac 75g, intramuscular amikacin 500 mg, and oral ciprofloxacin
00 mg. Under local anesthesia (5 mL, 2% Xylocaine injec-ion) and using US guidance, the dominant cysts were local-zed and punctured with an 18.5-gauge, three-piece, 20-cm-ong percutaneous nephrostomy puncture needle. Afterspiration, a maximum of 60 mL of absolute ethanol was in-ected in one cyst to ensure US-confirmed partial redistensionf the cyst. In a single session, a maximum of up to threeominant cysts were punctured, and care was taken not toxceed the safe (toxic) limit of ethanol.
The actual volume of ethanol injected was arrived at usingwo guiding principles: estimating the mean cyst volume onS (assuming it to be a spheroid) and estimating the cyst fluidolume actually aspirated after near total collapse of the cyst.he initial clinical endpoint was US evidence of partial cystistension. The cutoff value of 60 mL was used to ensureinimal systemic toxicity and allow the procedure to be done
n an outpatient basis. However, in absolute terms, particu-arly for some of the larger cysts, this resulted in replacing onlyne half the cyst volume. In the case of bilateral, large, symp-omatic cysts, the procedure was done on one side at a time.he aspirated cyst fluid was sent for cytologic examination inll the cases.
The pain sensation was quantified in a subjective mannersing the visual analog pain score on a scale of 1 to 10 at threeoints (before the procedure and 1 and 7 days after the proce-ure). Table I depicts the salient patient parameters. After ahort outpatient hospitalization, the patients were dischargedhe same evening with the advice to attend the follow-up clinicnd to continue taking oral ciprofloxacin 500 mg twice dailyor 3 days and oral diclofenac sodium 50 mg twice daily for 1ay. Follow-up US and urinalysis were scheduled at 2 weeks,months, and 6 months, and 1 year. Repeat sessions, if re-
uired, were scheduled after a 2-week interval. The need forxtra sessions was determined by the lack of symptomaticelief and US evidence of dominant cyst recurrence.
RESULTS
The mean patient age was 35.5 years (male/fe-ale ratio �3:2). All had at least two dominant
ysts; three, four, and five dominant cysts wereresent in 5, 1, and 1 patient, respectively. Theean cyst size was 7.43 cm, and an average of 48.5L of absolute ethanol was used per patient. In 2
atients, the procedure was done bilaterally, oneide at a time. All patients felt a burning pain in theank almost immediately after the injection andypically completely diminished in the next 2 to 4ours. Partial cyst regression from 9.5 to 5.5 mL42%) and from 8.5 to 4.5 mL (47%) was presentith recurrence in 2 patients (13.33%), and flank
ain persisted or was aggravated in 1 patient. One rROLOGY 68 (3), 2006
atient developed a nephrocutaneous fistula dis-harging pus in the ipsilateral flank that was man-ged conservatively with antibiotics and dailyressing and healed within 3 months. Clinicallyignificant urinary tract infection developed in 1atient and was successfully managed conserva-ively. The cytology of the aspirated cyst fluid waseported as normal in all cases.Figure 1 shows the serial ultrasound scans of 1
atient in whom the cyst had completely disap-eared, with the patient relieved of the agonizingank pain. Overall, no mortality occurred, andorbidity was limited to 20%. All but 2 patientsere treated on an outpatient basis. During the
ollow-up period, no major complications oc-urred. The mean hospitalization was 10.2 hours,nd the mean analgesic requirement was 250 mg oficlofenac sodium.The mean pretreatment and posttreatment se-
TABLE I. Salient patient dataatients (n) 15ominant cysts (n)Range 2–5Average 3.4
reoperative cyst volume (mL)Range 5.2–9.5Mean 7.11ean no. of sclerotherapy sessions/
patient1.33
olume of absolute ethanol used (mL)Range 30–70Mean 50.33
ecurrence rate (%) 3/15 (20)omplication rate (%) 2/15 (13.33)ure rate (%) 12/15 (80)ean analgesic requirement (mg of
diclofenac sodium)250
reoperative visual analog pain scoreRange 6–8Average 6.5
ostoperative visual analog painscore at 24 h
Range 5–6Average 5.5
ostoperative visual analog painscore at 1 week
Range 2–3Average 2.3ean preoperative serum creatinine
level (reference laboratory range1.4–1.8 mg/dL)
1.9
ean postoperative serum creatininelevel at 1 mo
2.1
ifference between baseline visual analog scale score and postprocedure score at 7ays significant at P � 0.05; difference between baseline and 1-day scores notignificant (analysis of variance with Tukey’s test; see Table II).ifference in creatinine values before and after procedure significant at P � 0.001
paired Student’s t test; see Table III).
um creatinine value was 1.89 and 2.1000 mg/
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L, respectively, at the end of 1 year (signifi-antly different at P �0.001 using the pairedtudent t test). The mean visual analogue paincores at the three points (scale 1 to 10) were 6.5t baseline and 5.5 and 2.3 at 1 and 7 days afterhe procedure, respectively (Tables I, II, and III).he difference between the baseline and 7-dayalues was significant at P �0.05), and the dif-erence between the 1-day and 7-day values wasot statistically significant (repeated measures ofnalysis of variance with Tukey’s test at the 5%
IGURE 1. Serial ultrasound scans of patient with ADcan. (B) CT scan. (C) Cyst aspiration with needle in cy
evel of significance) (Table II). t
84
COMMENT
ADPKD is an autosomal dominant disorder char-cterized by the presence of multiple renal corticalysts. Patients need to be regularly followed up andcreened for the occurrence of hypertension, renalnsufficiency, and flank pain, the most commonomplications of this hereditary disorder.1–3 Flankain is the most challenging chronic problem ands generally due to cyst distension, infection,nd/or obstructive uropathy.4 Although conserva-
and large dominant cyst. (A) Preoperative ultrasound) Six-month postoperative scan of sclerosed cyst.
PKD
ive therapy forms the mainstay for managing
UROLOGY 68 (3), 2006
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hronic pain, some patients with severe unrelent-ng flank pain and discomfort may respond only toeroofing of the larger cysts and sclerotherapy ofhe dominant cysts.4 Surgical or laparoscopic de-oofing is invasive and costly (because of the hos-italization and administration of general anesthe-ia) and, in the case of recurrence, repeat surgicalnterventions have limitations.
In contrast, sclerotherapy is a safe, simple, effec-ive, and minimally invasive therapeutic modalityith little or no morbidity that can alleviate the
hronic pain due to distended dominant cysts inDPKD. Also, in the case of recurrence, a repeateduncture is easy compared with repeated surgical/
TABLE II. Statistical analys
Type 3 Sum Squa
est of within-subjects contrasts*Source VAS
VAS1 vs. VAS2 13.067VAS2 vs. VAS3 153.600
Error VASVAS1 vs. VAS2 38.933VAS2 vs. VAS3 24.400
ests of between-subjectseffects†
Intercept 342.407Error 18.148
EY: VAS � visual analog scale (pain).ean baseline VAS score significantly different from mean 7-day VAS score at P � 0
ot significantly different from baseline VAS score.Repeated measures of analysis of variance with Tukey’s test at 5% level of significMeasure 1 (transformed variable: average).
TABLE III. Analysis of serum creatinine van Mean SD SEM C
aired samplestatisticswithpairedStudent’st test
PreoperativesCr
15 1.8933 0.14376 0.03712
PostoperativesCr
15 2.1000 0.13628 0.03519
aired samplecorrelation
15
airedsamplestest
Pre- andpost-sCrdifference
�0.20667 0.11629 0.03003
EY: SD � standard deviation; SEM � standard error of the mean; CI � confidencMean difference between pre and post-sCr significantly different at P � 0.0001.
aparoscopic deroofing. Although several investi- c
ROLOGY 68 (3), 2006
ators have successfully performed sclerotherapyor solitary renal cysts, the published data regard-ng treatment of patients with ADPKD arecarce.5–9 Various sclerosing agents, such as abso-ute alcohol, 3% aethoxysclerol-(polidocanol),eta-emitting radionuclide (holmium-166-chi-osan-complex), erythromycin-procaine, butyl cy-noacrylate-iodized oil, povidone-iodine, 50% ace-ic acid, and minocycline hydrochloride, have beensed in the past for the management of renal cysts,ith varying success rates.We used absolute ethanol because it has a wide
afety margin, a strong antiseptic effect, and theapacity to safely sclerose the epithelial lining of
f pain scores at three points
df Mean Square FP
Value
1 13.067 4.699 0.0481 153.600 88.131 0.000
14 2.781 — —14 1.743 — —
1 342.07 264.143 0.00014 1.296
ean 1-day VAS score significantly different from mean 7-day VAS; mean 1-day VAS
for VAS analysis at three points); measure 1.
before and after renal cyst sclerotherapylation P Value 95% CI t df
656 0.008
0.000* �0.27107 to�0.14227
6.883 14
al; sCr � serum creatinine.
is o
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ance (
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yst wall without damaging the renal parenchyma;
485
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an be safely repeated with no long-term seriouside effects or sequels10; and was economical to usen our setting.
In cases in which greater volumes of absolutethanol (more than 100 mL) are needed to ablatearger cysts, it is prudent that this be done only if anlcohol breath analyzer (not available in our hos-ital) is available to detect significant toxicity forloser monitoring. Also, overnight admissionhould be arranged. “Legal ethanol intoxication”ould entail a blood ethanol level of �80 mL; cog-itive and behavioral changes would start to ap-ear at just 20 to 30 mL, which translates to aboutne or two drinks.11 Because we performed theblation as an outpatient procedure, for safety rea-ons we used the limit of 60 to 70 mL (as this wasirectly injected into the renal cyst, it was assumedhat 90% to 100% was likely to be absorbed). Weuggest that ethanol dose titration with an alcoholreath analyzer should be done in each and everyase to increase the safety factor. In the presenttudy, we did not encounter any toxicity becausee never used doses in excess of 60 to 70 mL (as weanted to keep the procedure an outpatient one)
n any of our patients in a single session.Other sclerotic agents are either effective only in
maller cysts, may not be safe for repeated use, andre prone to a greater incidence of septic compli-ations. The sclerosing effect of absolute alcoholesults from the immediate denaturation of cellrotein on contact, resulting in cell fixation andevitalization within a few minutes and to intracel-ular dehydration and sclerosis of the cyst wall withrolonged contact.12
We were able to successfully ablate the dominantysts with absolute ethanol in most of our patientsecause of preselection; use of a multiple cystuncture aspiration technique with one or moreessions and an equal volume of absolute ethanolo partially redistend the cyst to enable cyst walllobal cell necrosis/sclerosis; and multiple injec-ions at the same or additional sessions to enable aonger contact period of the cyst wall with alcoholtheoretically associated with a lower recurrence
TABLE IV. Published cases of adult polycystsclero
uthorPatients
(n)DominantCysts (n)
SyImp
ee et al.,5 2003 11 —im et al.,6 2003 14 48
emasu et al.,8
199610 —
resent study 15 3.4/patient
ata in parentheses are percentages.
ate).12 s
86
No percutaneous drainage catheters were usedecause we used a multiple puncture aspirationnjection technique and all the patients werelosely followed up with serial US to ensure thebsence of urinoma or cyst fluid extravasation.omplete collapse with fibrosis of the cyst wall was
aken as the final endpoint. The only limitation tosing absolute ethanol we encountered was the oc-urrence of a brisk intense agonizing pain immedi-tely after injection; however, premedicating allur patients with an intramuscular injection of di-lofenac sodium 50 mg minimized this. Some pa-ients complained of a momentary episode of ver-igo and dizziness after ethanol injection; however,his subsided shortly afterward in all patients. Thisas probably related to the systemic effect of alco-ol absorption. Table IV provides the outcomes ofther reported studies of cyst sclerotherapy per-ormed for ADPKD by other investigators.
Renal cyst sclerotherapy should not be the initialherapeutic option for patients with ADPKD withomplicated or indeterminate cysts, hyperdenseultiseptated or infected (septic) cysts, parapelvic
ysts, uncontrolled hypertension, active hematu-ia, active sepsis or urinary tract infection, severehronic renal failure, cysts with CT or IVU evi-ence of intercommunication or direct communi-ation with the pelvicaliceal system; or cysts with auspicious cytology or tumor.13 We were able toeticulously screen all our patients before therapysing US, CECT, and US-guided aspirated cystuid cytology. This ensured that all patients werereselected according to our criteria and only thoseith Bosniak type 1, large, dominant cysts quali-ed for this study.Although in our experience, multiple injections
f pure ethanol were effective in eliminating theain due to dominant cysts in selected patientsith ADPKD, no significant improvement oc-
urred in renal function at the end of the first year.he change in pain scores from baseline to day 7as statistically significant using repeated-mea-
ures analysis of variance and Tukey’s test at the% significance level (Table II), and the change in
idney disease treated by cyst aspiration andrapyomaticment (n)
Recurrence(n) Sclerosing Agent
(63) 3 (36.6) Absolute ethanol(86) 2 (14) n-Butyl cyanoacrylate and
iodized oil (1:2 ratio)— Minocycline hydrochloride
(10 mg/dL)33 3 (20) 99% Ethanol
ic kthemptrove
712
—
1.
erum creatinine was statistically significant at P
UROLOGY 68 (3), 2006
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0.001 (Table III). Although the former suggestshat selective ablation of larger symptomatic cystsn patients with ADPKD using absolute ethanol is aalid therapeutic option for managing the chronicain not relieved by conservative therapy and opi-tes resulting from the dominant cysts, the latterhange possibly indicates the slow inevitable pro-ression of the disease.
CONCLUSIONS
Our limitations included the small number ofatients, the lack of a control group, the omissionf renal biopsy and lack of histologic evidence ofyst sclerosis, and the lack of an investigation ofhe long-term possible changes in blood pressure,enal function, and serum creatinine. Also, we ne-lected the extrarenal component of ADPKD inhis study. A larger number of patients and longerollow-up are required to completely define therecise role and long-term results of the effective-ess of pure alcohol sclerotherapy in select pa-ients with ADPKD with dominant cysts and pain.espite these limitations, we advocate that abso-
ute alcohol is an effective and safe sclerosing agenthat can be used safely as an initial, therapeutic,inimally invasive, outpatient option in select pa-
ients with ADPKD to alleviate the chronic painue to one or more dominant cysts. Repeated mul-iple sessions may be required to achieve a moreurable response.
REFERENCES1. Gabow PA: Autosomal dominant polycystic kidney dis-
ase. N Engl J Med 329: 332–342, 1993.2. Kumar S, Kimberling WJ, Gabow PA, et al: Exclusion of
utosomal dominant polycystic kidney disease type IIADPKD2) from 160 cM of chromosome 11. J Med Genet 27:97–700, 1990.
3. Gonzalo A, Rivera M, Quereda C, et al: Clinical featuresnd prognosis of adult polycystic kidney disease. Am J Neph-ol 10: 470–474, 1990.
4. Hemal AK, Gupta NP, Rajeev TP, et al: Retroperitoneo-copic management of infected cysts in adult polycystic kid-ey disease. Urol Int 62: 40–43, 1999.
5. Lee YR, and Lee KB: Ablation of symptomatic cystssing absolute ethanol in 11 patients with autosomal-domi-ant polycystic kidney disease. Korean J Radiol 4: 239–242,003.
6. Kim SH, Moon MW, Lee HJ, et al: Renal cyst ablationith n-butyl cyanoacrylate and iodized oil in symptomaticatients with autosomal dominant polycystic kidney disease:reliminary report. Radiology 226: 573–576, 2003.
7. Kitoh C, Ibe N, Yamada K, et al: Patient with autosomalominant polycystic kidney disease undergoing CAPD com-licated by intracystic hemorrhage: successful treatment bylcohol sclerotherapy. Nephron 86: 362–363, 2000.
8. Uemasu J, Fujihara M, Munemura C, et al: Cyst sclero-herapy with minocycline hydrochloride in patients with au-osomal dominant polycystic kidney disease. Nephrol Dialransplant 11: 843–846, 1996.
9. Uemasu J, Fujiwara M, Munemura C, et al: Effects of
opical instillation of minocycline hydrochloride on cyst sizeROLOGY 68 (3), 2006
nd renal function in polycystic kidney disease. Clin Nephrol9: 140–144, 1993.10. Agostini S, Dedola GL, Gabbrielli S, et al: Percutaneous
reatment of simple renal cysts with sclerotherapy and ex-ended drainage. Radiol Med 108: 522–529, 2004.
11. Hanna RM, and Dahniya MH: Aspiration and sclero-herapy of symptomatic simple renal cysts: value of two injec-ions of a sclerosing agent. AJR Am J Roentgenol 167: 781–83, 1996.12. Hemal AK, Khaitan A, Iqbal S, et al: Renal cell carci-
oma in cases of adult polycystic kidney disease: changingiagnostic and therapeutic implications. Urol Int 64: 9–12,000.13. Schuckit MA: Alcoholism and drug dependency, in
auci SA, Martin JB, Braunwald E, et al (Eds): Harrison’s Prin-iples of Internal Medicine, 14th ed. New York, McGraw-Hill,998, pp 2503–2504.
EDITORIAL COMMENTThe authors present a small experience of 15 patients with
DPKD who underwent percutaneous aspiration and ethanolclerosis of dominant renal cysts for the management of pain.onsistent with the continuing search for increasingly mini-ally invasive management strategies, the authors report a
echnique that can be performed under intravenous sedation.n this regard, the authors should be congratulated becauseatients undergoing a “moderately invasive” approach such asaparoscopic cyst decortication require general anesthesia andrequently have peritoneal symptoms that can last severaleeks.However, it is important to note that 2 patients (13%) in this
eries had significant complications, including one with aorsening of pain and another with a nephrocutaneous fistula
hat required 3 months to resolve. Additionally, although theuthors used analog pain scales to nicely document a signifi-ant decrease in pain 1 week after the procedure, no longererm data were presented. Also, the serum creatinine levelsncreased after the procedure and remained elevated 1 yearater, and no data on the patients’ blood pressure were re-orted.In contrast, using laparoscopic cyst decortication, Lee and
olleagues1 reported a durable pain response and improve-ent/stabilization in creatinine clearance of 3 years’ duration.Overall, the presented technique of cyst aspiration and scle-
osis may be considered for very highly selected patients withevere pain due to ADPKD who are not surgical candidates.owever, until more data become available, cyst aspiration
nd sclerosis in this setting should not be considered a first-ine treatment option.
REFERENCE1. Lee DI, Andreoni CR, Rehman J, et al: Laparoscopic cyst
ecortication in autosomal dominant polycystic kidney dis-ase: impact on pain, hypertension, and renal function. J En-ourol 17: 345–354, 2003.
Jaime Landman, M.D.Department of Urology
Columbia UniversityNew York, New York
doi:10.1016/j.urology.2006.07.001© 2006 ELSEVIER INC.
ALL RIGHTS RESERVED
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